Pyroglutamic aciduria: Studies on the enzymic block and on the metabolic origin of pyroglutamic acid

Abstract

A 20-year-old mentally retarded male with pyroglutamic aciduria has recently been described. The laboratory findings in this disorder are a high pyroglutamic acid (pyrrolidone-2-carboxylic acid) excretion (25-35 g/24 h), low excretion of urea (5-10 g/24 h) and metabolic acidosis. The serum and the cerebrospinal fluid contain 5 and 30 mg/100 ml, respectively, of pyroglutamic acid. The serum level of proline is 3 times the normal. Biochemical studies of the disorder show that (a) the patient converts ammonia to urea in a normal manner and responds normally to a high-calorie, low-protein diet. (b) A correlation exists between urinary ammonia and pyroglutamic acid, the excretion of both being independent of urinary pH. (c) Neither glutamine nor glutamic acid are direct precursors of pyroglutamic acid. (d) The patient, in contrast to normals, is unable to hydrolyze pyroglutamic acid to glutamic acid, (e) That i.v. infusion of amino acids to the patient is the only condition found which significantly increases the excretion of pyroglutamic acid. These studies indicate that pyroglutamate is involved in the renal handling of amino acids, and that the patient has a block in one of the steps (pyroglutamic acid to glutamic acid) of the γ-glutamyl cycle proposed by Orlowski and Meister. © 1972.